A Mendelian randomization study of depression and risk of cervical cancer (抑郁和宫颈癌发病风险相关的孟德尔随机化分析)

Abstract

Objective To explore the causal relationship between depression and the risk of cervical cancer by Mendelian randomization(MR). Methods Based on Genome Wide Association Study(GWAS) data, single nucleotide polymorphism(SNP) associated with depression were selected as genetic instrumental variables. Three Mendelian randomization methods, inverse variance weighted analysis(IVW), weighted median methods and MR-Egger were used to investigate the causal association between DP and the risk of cervical cancer. Radial MR was used to identify outliers. The analysis results were shown by odds ratio(OR)and 95% confidence interval(CI), and the effect was statistically significant with P＜0. 05. Results Totally 57 SNPs related to depression were included. The result of IVW show that depression was a risk factor for the risk of cervical cancer(OR=1. 002, 95%CI: 1. 0002～1. 003, P=0. 03). Weighted median method and MR-Egger provided the similar result. Sensitivity analysis found that no single SNP was strongly or reversely driving the overall effect for causal estimates. Conclusion Depression was a risk factor of cervical cancer. Strengthening the screening and prevention of cervical cancer in DP patients was of great significance to reduce the incidence of cervical cancer in this population. (目的 通过孟德尔随机化(MR)方法, 探究抑郁与宫颈癌发病风险的因果关联。方法 以全基因组关联分析研究(GWAS)数据为基础, 筛选出与抑郁的关联单核苷酸多态性(SNP)作为基因工具变量, 利用逆方差加权分析方法(IVW)、加权中值方法和 MR-Egger 方法三种孟德尔随机化方法探究抑郁与宫颈癌发病风险的因果关联。采用Radial MR用来识别异常值。分析结果以比值比(OR)和 95%可信区间(CI)显示, P＜0. 05 为效应具有统计学意义。结果 共筛选到57个与抑郁相关的SNP。 IVW 结果显示, 抑郁是宫颈癌发病风险的危险因素［OR=1. 002, 95%CI (1. 0002～1. 003), P=0. 03］; 加权中值法和 MR-Egger 效应估计值具有相似的统计结果。敏感性分析发现没有对因果估计结果产生较大的 SNP。结论 抑郁是宫颈癌发病风险的危险因素, 加强抑郁患者宫颈癌的筛查、预防以及健康宣教, 对于降低该人群的宫颈癌发病率具有重要意义。)

Keywords

• depression
• mendelian randomization
• cervical cancer
• screening
• health education
• 抑郁
• 孟德尔随机化
• 宫颈癌
• 筛查
• 健康宣教